Weight loss and functional decline in older Japanese people: A cohort study using large-scale claims data.

BACKGROUND: The association between weight loss and subsequent functional decline is uncertain. The study aims to elucidate the association between weight loss over a year and subsequent functional decline requiring assistance in performing their activities of daily living in older individuals. METHODS: The study used data from the publicly funded Long-Term Care Insurance service in Japan, which provides coverage for long-term care services for individuals unable to perform activities of daily living due to physical or cognitive impairment. The study enrolled people born in or before 1949, who underwent health checkups in both 2014 and 2015. The participants were followed from 2015 to the worsening of functional decline requiring long-term care services, death, or February 28, 2019, whichever occurred first. The risk of subsequent functional decline in each weight loss category was estimated using a Cox regression model adjusted for age, sex, baseline body mass index, smoking, and Charlson comorbidity index. RESULTS: We identified 67,452 eligible individuals from the database. The median follow-up period was 1,284 days. The hazard ratios (95 % confidence interval) of functional decline for -1 %, -2 %, -3 %, -4 %, and ≤-5% weight change compared to 0 % weight change were 1.17 (1.03-1.32), 1.26 (1.11-1.43), 1.29 (1.12-1.49), 1.61 (1.39-1.87), and 1.79 (1.58-1.99), respectively. CONCLUSIONS AND IMPLICATIONS: Older people with weight loss of 1 % or more were at risk of functional decline. Close weight monitoring may serve as an easy and inexpensive means of identifying older individuals at risk of functional decline.

Saturation of Percutaneous Oxygen Decreases with Meal Consumption in Patients with Acute Pneumonia.

OBJECTIVE: This study aimed to investigate how respiratory status may be affected during meal consumption in patients with acute pneumonia, mainly aspiration pneumonia, using percutaneous oxygen saturation (SpO2) and pulse rate (PR) measurements. METHODS: We recruited 44 inpatients at the Towada City Hospital and divided them into 'pneumonia' and 'control' groups. Generalized linear mixed effects model was used for analysis. The pneumonia group comprised 22 patients (mean age 81.2 ± 7.0 years, body mass index [BMI] 21.1 ± 4.0 kg/m2) with 1-3 points A-DROP scores. The control group comprised 22 patients (mean age 80.5 ± 4.9 years, BMI 20.9 ± 2.9 kg/m2) with no obvious respiratory diseases. SpO2 and PR were measured 30 min before, during, and 30 min after meals. RESULTS: SpO2 was significantly lower during meals in the pneumonia group (-1.60%; 95% confidence interval = -2.76 to -0.44). There were no significant changes in PR during or after meals in the pneumonia group. CONCLUSIONS: This study suggests pneumonia may worsen respiratory status during meal intake. Patients with pneumonia may be unable to eat adequately due to worsened oxygenation during meals, even in the absence of aspiration. Therefore, it is important to observe whether there is a decrease in respiratory status during meals.

Risk of post-extraction bleeding with direct oral anticoagulant compared with warfarin: Retrospective cohort study using large scale claims data in Japan.

INTRODUCTION: Comparative safety of direct oral anticoagulants vs. warfarin in patients undergoing tooth extraction remains unclear. We compared the incidence of post-extraction bleeding between patients taking warfarin and those taking direct oral anticoagulants (DOACs) using administrative claims data. MATERIALS AND METHODS: We identified outpatients on anticoagulant therapy who underwent permanent tooth extraction between 2015 and 2020 and categorized them into the warfarin and DOAC groups based on medication prescribed within six months prior to tooth extraction. We used the overlap propensity score weighting method to balance the baseline characteristics between the groups and compared the incidence of post-extraction bleeding within seven days after tooth extraction. RESULTS: Among 5253 eligible patients, those in the DOAC group (n = 3696) were older and less frequently prescribed antiplatelets than those in the warfarin group (n = 1557). The distribution of tooth extraction type and number of teeth extracted in a single procedure did not differ between the groups. The unadjusted incidences of post-extraction bleeding in the warfarin and DOAC groups were 35 (2.2 %) and 71 (1.9 %), respectively. Moreover, the overlap weighting analysis showed that the adjusted odds ratio of post-extraction bleeding in the DOAC group in comparison with that in the warfarin group was 0.84 (95 % confidence interval, 0.54-1.31). CONCLUSION: The incidence of post-extraction bleeding in patients taking DOACs was comparable to that in patients taking warfarin. The findings suggest that dentists and physicians should exercise the same degree of caution when extracting teeth in patients on DOACs and those on warfarin in terms of post-extraction bleeding.

Complete Lateral Positioning Enabled Feeding in a Patient with Aspiration Pneumonia.

The complete lateral position can be used to widen the lateral pharynx in a direction that facilitates swallowing and reduces the risk of aspiration, even if the patient is unable to eat in the sitting position. Here, we report a case of aspiration pneumonia in a patient who was unable to eat in the sitting position after swallowing endoscopy, but was able to eat in the complete lateral position. By employing complete lateral positioning, more patients may be able to continue oral intake.

Implications for clinical dental practice during the coronavirus disease pandemic: A scoping review.

PURPOSE: It is over a year since the first case of coronavirus disease (COVID-19) was confirmed in China. This paper reviews and summarizes the characteristics of COVID-19, as understood of December 2020, from a dental perspective. STUDY SELECTION: The PubMed and Scopus online databases were searched using a combination of free words and Medical Subject Headings terms: "dentist" OR "oral care" AND "COVID-19" OR "SARS-CoV-2." RESULTS: Older people and those with underlying medical conditions have an increased risk of serious illness due to COVID-19. The virus enters the body by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. It is common for people with COVID-19 to have mild or no symptoms. Moreover, the disease is not contagious in most infected people; it is only highly contagious in some infected people, thereby forming clusters. Due to the large number of virus particles that are shed prior to the onset of symptoms of the disease, retrospective surveys are important. Appropriate personal protective equipment against corona vortices is also important in clinical practice. Although polymerase chain reaction tests are useful for confirming infection in suspected individuals, their reliability is questionable. In addition, concerns regarding long-term sequelae have been reported. CONCLUSION: There are few high-quality reports on the implications of COVID-19 in dental practice. However, reports suggest that insufficient oral hygiene may be a risk factor for infection. Reports that ACE2 receptors are abundant in the oral cavity also suggest the importance of oral care.

Familial Mediterranean Fever with Psychiatric Disorder which Have not Been Diagnosed over 30 Years: A Case Report.

Familial Mediterranean fever (FMF) is an inherited autoimmune disease characterized by periodic fevers and serositis. Most cases have been diagnosed within 10 years or less; however, there have been no reports of cases in which diagnosis was delayed for several decades. In this study, we encountered a case of FMF in which the patient had recurrent unexplained fevers since childhood, but diagnosis was delayed for more than 30 years due to a psychiatric disorder. Our findings showed that a possible reasons for this delay are possibility of neglect or parenting skills issues, little knowledge of FMF in Japan and the lack of social connections due to the patient's underlying mental illness. We suggest that it is important to conduct a thorough medical interview to identify FMF, as it may go undiagnosed, especially when the patient has few social ties.

Swallowing evaluation by the Kuchikara Taberu Balance Chart and videoendscopic examination reveals that respiratory conditions, chewing, and position are strongly related to dysphagia.

This study focused on the Kuchikara Taberu Balance Chart (KTBC) as a tool for swallowing function evaluation. To clarify the relationship between videoendoscopic (VE) examination of swallowing function and the KTBC, we compared median KTBC scores with and without laryngeal penetration identified by VE. Sixty-five patients with a mean age of 84.3 ± 7.9 years were examined at the Towada City Hospital. The patients were classified into groups based on laryngeal penetration, including 28 patients with and 37 patients without penetration. We found no significant differences in patient backgrounds. The median KTBC score (interquartile range) was 36.5 (31-44.5) in the group with laryngeal penetration and 42 (35-48.5) in the group without penetration, but the scores were not significantly different (level of statistical significance at α = 0.0036 determined by the Bonferroni correction method) when compared with the Mann-Whitney U test (36.5 vs. 42, z = -2.33, p = 0.020). The median respiratory condition (3 vs. 4, z = - 3.23; p < 0.0036), oral preparatory and propulsive phases (3 vs. 4, z = - 2.96; p < 0.0036), and position and endurance (1 vs. 3, z = - 3.25; p < 0.0036) scores were significantly lower in the group with laryngeal penetration. This study revealed a correlation between laryngeal penetration confirmed by VE and KTBC scores. Consequently, respiratory condition, oral preparatory and propulsive phases, and position and endurance may be useful as tools for the assessment of swallowing. In particular, we recommend adding respiratory status to dysphagia screening.

Characterization of Anti-Goat Podoplanin Monoclonal Antibody PMab-235 Using Immunohistochemistry Against Goat Tissues.

Podoplanin (PDPN)/T1alpha is expressed on lymphatic endothelial cells, type I alveolar cells of the lungs, and podocytes of the kidney. PDPN possesses three platelet aggregation-stimulating (PLAG) domains (PLAG1, PLAG2, and PLAG3) of the N-terminus and the PLAG-like domains (PLDs). We previously reported an anti-goat PDPN (gPDPN) monoclonal antibody (mAb), PMab-235, which was developed using the Cell-Based Immunization and Screening (CBIS) method. PMab-235 is very useful in flow cytometry, Western blotting, and immunohistochemical analyses; however, the binding epitope of PMab-235 remains to be elucidated. In this study, we investigated the epitopes of PMab-235 using enzyme-linked immunosorbent assay and immunohistochemistry. The results revealed that the critical epitope of PMab-235 produced by CBIS method is Arg75, Leu78, and Pro79 of gPDPN, which is included in PLD. The findings of our study can be applied to the production of more functional anti-gPDPN mAbs.

Epitope Mapping of Antipig Podoplanin Monoclonal Antibody PMab-213.

Podoplanin (PDPN), a type I transmembrane sialoglycoprotein, is expressed on lymphatic endothelial cells, podocytes of the kidneys, and type I alveolar cells of the lungs. PDPN, a platelet aggregation-inducing factor, comprises three platelet aggregation-stimulating (PLAG) domains (PLAG1, PLAG2, and PLAG3) in the N-terminus and PLAG-like domains in the middle of the PDPN protein. We have previously reported a mouse antipig PDPN (pPDPN) monoclonal antibody (mAb) clone, PMab-213, which was developed using the Cell-Based Immunization and Screening (CBIS) method. PMab-213 is very useful in flow cytometry, Western blotting, and immunohistochemical analyses; however, the binding epitope of PMab-213, which was developed by CBIS method, remains to be elucidated. Therefore, this study aimed to investigate the epitope of PMab-213 using enzyme-linked immunosorbent assay, flow cytometry, and immunohistochemical analyses. The results revealed that the critical epitopes of PMab-213 are Pro53, Arg54, Arg56, and Tyr60 of pPDPN.

PMab-235: A monoclonal antibody for immunohistochemical analysis against goat podoplanin.

Sensitive and specific monoclonal antibodies (mAbs) against not only human but also mouse, rat, rabbit, dog, cat, bovine, pig, and horse podoplanins (PDPNs) have been established in our previous studies. However, anti-goat PDPN (gPDPN) has not been established yet. PDPN has been utilized as a lymphatic endothelial cell marker especially in pathological diagnoses; therefore, mAbs for immunohistochemical analyses using formalin-fixed paraffin-embedded tissues are needed. Although we recently demonstrated that an anti-bovine PDPN mAb, PMab-44 cross-reacted with gPDPN, PMab-44 did not detect lymphatic endothelial cells in immunohistochemistry. In this study, we immunized mice with gPDPN-overexpressing Chinese hamster ovary (CHO)-K1 (CHO/gPDPN) cells, and screened mAbs against gPDPN using flow cytometry. One of the mAbs, PMab-235 (IgG1, kappa), specifically detected CHO/gPDPN cells by flow cytometry. Furthermore, PMab-235 strongly detected lung type I alveolar cells, renal podocytes, and lymphatic endothelial cells of colon by immunohistochemistry. These findings suggest that PMab-235 may be useful as a lymphatic endothelial cell marker for goat tissues.

Immunohistochemical Analysis of the Harbor Porpoise Using Antipodoplanin Antibody PMab-237.

Podoplanin (PDPN)/T1 alpha is known as a specific marker of lymphatic endothelial cells and type I alveolar cells. Sensitive and specific monoclonal antibodies (mAbs) for PDPN are needed for immunohistochemical analyses. Recently, we developed an anticetacean PDPN mAb, PMab-237. Herein, immunohistochemical analyses showed that PMab-237 strongly detected pulmonary type I alveolar cells, renal podocytes, and lymphatic endothelial cells of the harbor porpoise. These findings suggest that PMab-237 may be useful for immunohistochemical analyses for cetacean tissues.

Establishment of an Anticetacean Podoplanin Monoclonal Antibody PMab-237 for Immunohistochemical Analysis.

Podoplanin (PDPN) has been utilized as a lymphatic endothelial cell marker especially in pathological diagnoses. Therefore, sensitive and specific monoclonal antibodies (mAbs) targeting PDPN are needed for immunohistochemical analyses using formalin-fixed paraffin-embedded tissues. Recently, anti-PDPN mAbs against many species, such as human, mouse, rat, rabbit, dog, cat, bovine, pig, and horse were established in our studies. However, anticetacean (whale) PDPN (wPDPN) has not been established yet. In this study, we immunized mice with wPDPN-overexpressing Chinese hamster ovary (CHO)-K1 (CHO/wPDPN) cells, and screened mAbs against wPDPN using flow cytometry. One of the mAbs, PMab-237 (IgG1, kappa), specifically detected CHO/wPDPN cells by flow cytometry and immunohistochemistry. Our findings suggest the potential usefulness of PMab-237 for the functional analyses of wPDPN.

Anti-Human Epidermal Growth Factor Receptor 2 Monoclonal Antibody H2Mab-41 Exerts Antitumor Activity in a Mouse Xenograft Model of Colon Cancer.

The expression of human epidermal growth factor receptor 2 (HER2) has been reported to be overexpressed in several cancers, such as breast, lung, gastric, pancreatic, and colorectal cancers, and be associated with poor clinical outcomes. Trastuzumab, a humanized anti-HER2 antibody, provides significant survival benefits for patients with HER2-overexpressing breast cancers and gastric cancers. In this study, we developed a novel anti-HER2 monoclonal antibody (mAb), H2Mab-41 (IgG2b, kappa), and the antitumor activity of H2Mab-41 was investigated using mouse xenograft models. Caco-2 cells (human colon cancer cell line), which expresses HER2, were subcutaneously implanted into the flanks of nude mice. H2Mab-41 and control mouse IgG were injected three times into the peritoneal cavity of mice. H2Mab-41 significantly reduced tumor development of Caco-2 xenograft in comparison with the control mouse IgG on days 5, 8, 11, 15, and 19. Taken together, these results suggest that H2Mab-41 is useful for antibody therapy against HER2-expressing colon cancers.

Epitope Mapping of Anti-Diacylglycerol Kinase ζ Monoclonal Antibody for the Detection of T Cells by Immunohistochemical Analyses.

The diacylglycerol kinases (DGKs) are a family of proteins that catalyze the phosphorylation of the cell membrane lipid diacylglycerol (DG), a cellular component that is important in lipid biochemistry and signal transduction, into phosphatidic acid. DG-mediated signal transduction downstream of the T cell receptor has previously been reported to be terminated in most cases by one of 10 DGK isoforms, DGKζ. In this study, we performed immunohistochemical analysis using a rabbit anti-DGKζ monoclonal antibody (mAb) (clone EPR22040-80) against tissues from the tonsils of a patient with oropharyngeal squamous cell carcinoma. We demonstrated that many DGKζ-expressing T cells are localized in the tonsils. We further characterized the binding epitope using an enzyme-linked immunosorbent assay and found that Pro790, Gln791, Gly792, and Leu795 residues of DGKζ are important for facilitating anti-DGKζ mAb binding to DGKζ. This anti-DGKζ mAb could be valuable in immunohistochemical analyses in determining the distribution of DGKζ-expressing T cells in pathophysiological tissues.

Epitope Mapping of Anti-Tiger Podoplanin Monoclonal Antibody PMab-231.

Podoplanin (PDPN) is expressed on podocytes of the kidneys, type I alveolar cells of the lungs, and lymphatic endothelial cells. PDPN comprises three platelet aggregation-stimulating (PLAG) domains (PLAG1, PLAG2, and PLAG3) in the N-terminus and PLAG-like domains in the middle of the PDPN protein. We have previously reported on an anti-tiger PDPN (tigPDPN) monoclonal antibody (mAb), PMab-231, which was developed using the Cell-Based Immunization and Screening (CBIS) method. PMab-231 is very useful in flow cytometry, Western blotting, and immunohistochemical analyses; however, the binding epitope of PMab-231 remains to be elucidated. This study aimed to investigate the epitopes of PMab-231, which was developed by CBIS method, using enzyme-linked immunosorbent assay. The results revealed that the critical epitopes of PMab-231 are Glu29, Asp30, Asp31, Ile32, Met33, Thr34, Pro35, Gly36, and Glu38 of tigPDPN, which is corresponding to PLAG1/2. The findings of our study can be applied to the production of more functional anti-tigPDPN mAbs.

Epitope Mapping of the Antihorse Podoplanin Monoclonal Antibody PMab-202.

Horse podoplanin (horPDPN), a type I transmembrane sialoglycoprotein, is expressed on the podocytes of the kidneys, alveolar type I cells of the lungs, and lymphatic endothelial cells. PDPN is a platelet aggregation-inducing factor, and it primarily possesses three platelet aggregation-stimulating (PLAG) domains, that is, PLAG1, PLAG2, and PLAG3, at the N-terminus and several PLAG-like domains. In a previous study, we reported on a mouse anti-horPDPN monoclonal antibody (mAb) clone, PMab-202. Although the effectiveness of PMab-202 in flow cytometry and Western blotting is known, its exact binding epitope remains unknown to date. In this study, enzyme-linked immunosorbent assay and flow cytometry were used to identify the epitope of PMab-202. We found that the critical epitopes of PMab-202 include Lys64, Thr66, and Phe70 of horPDPN. We believe that our findings can be applied in the production of more functional anti-horPDPN mAbs.

Establishment of a monoclonal antibody PMab-233 for immunohistochemical analysis against Tasmanian devil podoplanin.

Monoclonal antibodies (mAbs) against not only human, mouse, and rat but also rabbit, dog, cat, bovine, pig, and horse podoplanins (PDPNs) have been established in our previous studies. PDPN is used as a lymphatic endothelial cell marker in pathological diagnoses. However, mAbs against Tasmanian devil PDPN (tasPDPN), which are useful for immunohistochemical analysis, remain to be developed. Herein, mice were immunized with tasPDPN-overexpressing Chinese hamster ovary (CHO)-K1 (CHO/tasPDPN) cells, and hybridomas producing mAbs against tasPDPN were screened using flow cytometry. One of the mAbs, PMab-233 (IgG1, kappa), specifically detected CHO/tasPDPN cells by flow cytometry and recognized tasPDPN protein by western blotting. Furthermore, PMab-233 strongly detected CHO/tasPDPN cells by immunohistochemistry. These findings suggest that PMab-233 may be useful as a lymphatic endothelial cell marker of the Tasmanian devil.

Establishment of a monoclonal antibody PMab-225 against alpaca podoplanin for immunohistochemical analyses.

Podoplanin (PDPN) is known as a lymphatic endothelial cell marker. Monoclonal antibodies (mAbs) against human, mouse, rat, rabbit, dog, cat, bovine, pig, and horse PDPN have been established in our previous studies. However, mAbs against alpaca PDPN (aPDPN), required for immunohistochemical analysis, remain to be developed. In the present study, we employed the Cell-Based Immunization and Screening (CBIS) method for producing anti-aPDPN mAbs. We immunized mice with aPDPN-overexpressing Chinese hamster ovary (CHO)-K1 cells (CHO/aPDPN), and hybridomas producing mAbs against aPDPN were screened using flow cytometry. One of the mAbs, PMab-225 (IgG2b, kappa), specifically detected CHO/aPDPN cells via flow cytometry and recognized the aPDPN protein on Western blotting. Further, PMab-225 strongly stained lung type I alveolar cells, colon lymphatic endothelial cells, and kidney podocytes via immunohistochemistry. These findings demonstrate that PMab-225 antibody is useful to investigate the function of aPDPN via different techniques.

Anti-CD133 Monoclonal Antibody CMab-43 Exerts Antitumor Activity in a Mouse Xenograft Model of Colon Cancer.

Cancer stem cells contribute to tumorigenesis, metastasis, recurrence, and chemoresistance. CD133/prominin-1-a pentaspan membrane glycoprotein-has been used as a stem cell biomarker for the isolation of stem-like cells from a variety of normal and pathological tissues. In our previous studies, we developed several anti-CD133 monoclonal antibodies using Cell-Based Immunization and Screening (CBIS) methods, followed by characterization of their efficacy by flow cytometry, western blotting, and immunohistochemical analyses. One of the 100 clones, CMab-43 (IgG2a, kappa), demonstrated a sensitive and specific reaction against colon cancer cells. This study aimed to investigate the antitumor activity of CMab-43. Caco-2 cells (human colon cancer cell line) were subcutaneously implanted into the flanks of nude mice. CMab-43 and control mouse IgG were injected three times into the peritoneal cavity of mice. Tumor formation was observed in the control and CMab-43-treated mice of Caco-2 xenograft models. CMab-43 significantly reduced tumor development of Caco-2 xenograft in comparison with the control mouse IgG on days 12, 14, and 17. Our results cumulatively suggest that CMab-43 is useful for antibody therapy against CD133-expressing colon cancers.